Using a variety of biochemical, structural, and molecular and cell biological approaches, we are studying the molecular mechanisms underlying the diverse array of cellular functions involving DNA repair proteins. Surface plasmon resonance studies allow us to monitor in real-time key protein-protein and protein-DNA interactions formed in vitro under a variety of conditions to ask about complex stability and to characterize various aspects of complex formation utilizing both wild type and mutant proteins. Fluorescently tagged proteins and immunofluorescence microscopy are being used to study protein-protein interactions as well as traffic within different cell compartments. Modulation of the levels of repair proteins, post-translational modifications, and subcellular localization are being examined in response to a variety of genotoxic stresses. Single molecule studies using atomic force microscopy allow us to visualize multi-protein complexes bound to DNA lesions. These studies can help shed light on specific DNA repair pathways as well as general cellular responses to DNA damage that may be relevant to cancer and aging.